The goal of this research project is to identify molecular changes that are associated with the progression of a peripheral nerve sheath tumor (PNST) from benign to malignancy. Archival and prospectively acquired benign PNSTs and malignant PNSTs are collected, and molecular changes at the NF1 locus and throughout the genome are assessed. In addition, immunohistological evaluations of benign plexiform neurofibromas and malignant peripheral nerve sheath tumors are performed. We have begun preliminary analyses of immunohistochemical phenotypes of the tumors and genome-wide screen tetra-nucleotide screen for allelic imbalance, as a marker for accumulation of somatic mutations in PNSTs.

Nerve sheath tumors can be a significant cause of morbidity for many patients. These include benign tumors such as schwannomas, diffuse and plexiform neurofibromas, and atypical neurofibromas, as well as the aggressive soft tissue sarcoma known as the malignant peripheral nerve sheath tumor (MPNST). Nerve sheath tumors occur sporadically and in the context of the clinical neuro-genetic tumor predisposition syndromes neurofibromatosis type 1 (NF1) and type 2 (NF2). Historically, the mainstay of treatment for nerve sheath tumors has been surgery. However, for both benign and malignant nerve sheath tumors, there is a high recurrence rate, highlighting the pressing need for novel therapies. As we have entered the genomic era, the hope is that an improved understanding of the genetics, and therefore the biology, of these tumors will ultimately lead to therapies that result in better outcomes. In this Special Issue, we include both review articles and original research related to the genomic understanding and modeling of schwannomas, plexiform and diffuse neurofibromas, atypical neurofibromas, and malignant peripheral nerve sheath tumors as well as genomic methods being developed and applied to advance our understanding of these tumors.

Tumors involving peripheral nerves may be extremely challenging lesions to diagnose and treat. In order to optimize their management, physicians should have a thorough knowledge of peripheral nerve anatomy and pathology (both gross and microscopic), as well as familiarity with microsurgical techniques and intraoperative neurophysiological recording. This compendium deals with all aspects of tumors affecting peripheral nerves, from diagnosis to treatment; the topics it addresses range from epidemiology, anatomy, physiology, pathology, and clinical diagnosis to electrophysiology, imaging, genetic/cytomolecular aspects. Surgical approaches, biopsies and resection of various benign, malignant and pseudo-tumoral lesions, plexus tumors (both brachial and lumbosacral), and adjunctive treatment modalities and pain-related issues are described in detail. The book is intended not only for neurosurgeons, hand surgeons, plastic and orthopedic surgeons new to the field, but also for seasoned specialists who wish to update their knowledge with new insights based on robust experimental and clinical material. In addition, it will be a helpful tool for general and oncological surgeons who are sometimes faced with the treatment of mass lesions that may be potential nerve tumors, and for all practitioners who are engaged in the arduous struggle to bring relief to patients affected by these lesions.

This volume offers an update of the clinical signs, diagnostic criteria (including molecular diagnosis) and targeted therapies for a particular type of genodermatosis, providing a handy and unique tool for early diagnosis. In recent years, our understanding of genodermatosis and neurocutaneous syndromes has increased, but although Type 1 Neurofibromatosis (NF1) is the most common neuroectodermal disorder and involves a large number of patients and medical disciplines, this syndrome remains underestimated, often misdiagnosed thus leading to inaccurate treatment. The literature on the molecular and pathogenetic aspects is ample, but current clinical approaches, classification, diagnostic criteria and treatment protocols are outdated, creating difficulties in early diagnosis and treatment. As such, a chapter is devoted renewing current diagnostic criteria; it includes clinical and molecular data, to offer a sound, updated discussion basis for a consensus conference. NF1 is a “time-dependent” disorder, meaning that the onset of clinical signs are closely linked to patient age and the book discusses this particularly neglected aspect extensively, as well as the latest molecular diagnosis techniques, which are highly sensitive have not been included in the diagnostic criteria. It also explains the role of the RAS-MAPK pathway and genotype-phenotype correlations. In addition it explores new concepts concerning the pathogenesis of neurofibromas and other hamarthomas and their relevance for a modern therapeutical approach with targeted molecular drugs, as well as newly discovered aspects of NF1 in all internal organs, together with their diagnostic counterparts. A chapter on mosaic neurofibromatosis is also included. There is a particular focus on differential diagnosis (i.e. other diseases with café-au-lait macules), and the recently described Legius syndrome will be presented directly by Prof Eric Legius. All chapters are easy-to-understand, up-to-date, comprehensive and concise tools and are intended for a wide range of professionals involved with genetic disorders of the skin and neurocutaneous diseases: dermatologists, pediatricians, neurologists, oncologists and general practitioners.

Neurofibromatosis 1 (NF1) is an inherited neurocutaneous disease that has a major impact on the nervous system, eye, skin, and bone. Individuals with NF1 have a predisposition to benign and malignant tumor formation and the hallmark lesion is the neurofibroma, a benign peripheral nerve sheath tumor. The gene for NF1 was cloned on chromosome 17q11.2 and neurofibromin, the NF1 protein, controls cell growth and proliferation by regulating the proto-oncogene Ras and cyclic adenosine monophosphate (AMP). Advances in molecular biology and mouse models of disease have enhanced our understanding of the pathogenesis of NF1 complications and facilitated targeted therapy. Progress has been made in developing robust clinical and radiological outcome measures and clinical trials are underway for children with learning difficulties and for individuals with symptomatic plexiform neurofibromas.

The “neurofibromatoses” are a set of distinct genetic disorders that have in common the occurrence of tumors of the nerve sheath. They include NF1, NF2, and schwannomatosis. All are dominantly inherited with a high rate of new mutation and variable expression. NF1 includes effects on multiple systems of the body. The major NF1-associated tumor is the neurofibroma. In addition, clinical manifestations include bone dysplasia, learning disabilities, and an increased risk of malignancy. NF2 includes schwannomas of multiple cranial and spinal nerves, especially the vestibular nerve, as well as other tumors such as meningiomas and ependymomas. The schwannomatosis phenotype is limited to multiple schwannomas, and usually presents with pain. The genes that underlie each of the disorders are known: NF1 for neurofibromatosis type 1, NF2 for neurofibromatosis type 2, and INI1/SMARCB1 for schwannomatosis. Genetic testing is possible to identify mutations. Insights into pathogenesis are beginning to suggest new treatment strategies, and therapeutic trials with several new forms of treatment are underway.

Neurofibromatosis Type 1: New Insights for the Healthcare Professional: 2011 Edition is a ScholarlyPaper™ that delivers timely, authoritative, and intensively focused information about Neurofibromatosis Type 1 in a compact format. The editors have built Neurofibromatosis Type 1: New Insights for the Healthcare Professional: 2011 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Neurofibromatosis Type 1 in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Neurofibromatosis Type 1: New Insights for the Healthcare Professional: 2011 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.